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Antacid tablets

Image : Antacid tablets. By: Midnightcomm. License: CC BY 2.5

Overview of Acid Peptic Diseases

Acid peptic diseases are a group of disorders that involve erosion or ulceration of the mucosal lining of the gastrointestinal tract. Examples include gastroesophageal reflux disease (GERD), gastric and duodenal peptic ulcers, non-ulcer dyspepsia, and stress-related gastric mucosal injury. The use of NSAIDs (nonsteroidal anti-inflammatory drugs) and H. pylori infection account for approximately 90% of peptic ulcers.

Gastrointestinal Physiology

deep gastric ulcer

Image: Endoscopic image of deep gastric ulcer in the gastric antrum. By: Samir. License: CC BY-SA 3.0

A relative imbalance between damaging and defensive factors of the gastrointestinal mucosa is important in the pathogenesis of peptic ulcer disease (see image).

Damaging factors include acid, pepsin, bile, and NSAIDs, while defensive factors include mucus secretion, bicarbonate secretion, mucosal blood flow, prostaglandins, and repair processes following mucosal injury.

In the stomach, acid (H+) is secreted by the proton pump (H+/K+-ATPase) located on the canalicular surface of the parietal cells in the gastric mucosal lining.

The parietal cells contain receptors for histamine (H2 receptors), gastrin (CCK-B receptors), and acetylcholine (muscarinic M3 receptors). Their stimulation increases the secretion of acid by the parietal cells.

Stimulation of enterochromaffin (ECL) cells by gastrin and acetylcholine also releases histamine, which in turn stimulates parietal cells to secrete acid.

Drug Treatment


Mechanism of Action Class of Drugs Examples
Reduce gastric acidity Antacids Magnesium hydroxide, aluminum hydroxide, sodium bicarbonate, calcium carbonate
H2-receptor antagonists Cimetidine, ranitidine, famotidine, nizatidine
Proton pump inhibitors Omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole
Mucosal-protecting agents Sucralfate, misoprostol, bismuth compounds
Antibiotics Anti-H. pylori antibiotics Amoxicillin, clarithromycin, metronidazole, tinidazole


Antacids are weak bases that reduce gastric acidity by reacting with gastric hydrochloric acid (HCl) and thereby forming salt and water. Many antacids are available as over-the-counter formulations; however, the acid-neutralizing capacities of different formulations are highly variable.

Antacids should not be taken within two hours of the consumption of iron, tetracyclines, fluoroquinolones, and itraconazole, as they interfere with the absorption of these drugs.

Magnesium Hydroxide (Milk of Magnesia, Mg(OH)2)

  • Reacts with HCl to form magnesium chloride (MgCl2) and water.
  • Unabsorbed magnesium salts cause osmotic diarrhea.

Aluminum Hydroxide (Al(OH)3)

  • Reacts with HCl to form aluminum chloride (AlCl3) and water.
  • Unabsorbed aluminum salts have a constipating effect.

Due to the laxative and constipating effects of magnesium and aluminum salts, respectively, magnesium hydroxide and aluminum hydroxide are frequently combined in proprietary combinations.

Sodium Bicarbonate (NaHCO3)

  • Reacts with HCl to form sodium chloride and carbon dioxide
  • Carbon dioxide causes belching and gastric distension, while sodium chloride may worsen fluid retention in patients with hypertension, heart failureand renal failure.
  • Unreacted bicarbonate may produce metabolic alkalosis due to its ready absorption.
  • Excessive use of sodium bicarbonate along with an excessive intake of dairy products can cause hypercalcemia, renal failure, and metabolic alkalosis (milk-alkali syndrome).

Calcium Carbonate (CaCO3)

  • Calcium carbonate is less soluble than sodium bicarbonate and reacts slowly with HCl to form calcium chloride and carbon dioxide.
  • Important side effects include belching, metabolic alkalosis, and milk-alkali syndrome with excessive consumption of dairy products.

H2 Blockers (H2-receptor Antagonists)

H2 blockers competitively inhibit H2 receptors at gastric parietal cells and reversibly inhibit the secretion of acid in a dose-dependent manner. Importantly, they inhibit nocturnal acid secretion more effectively than meal-stimulated acid secretion.

All H2 blockers, except nizatidine, undergo significant first-pass hepatic metabolism. They are all (except nizatidine) available in intravenous-administration formulations. Famotidine is the most potent Hblocker. Dose reduction is required in moderate-to-severe renal insufficiency and in possibly severe hepatic insufficiency.

H2 blockers are very safe. Adverse effects include the following:

  • Headache, myalgia, fatigue, diarrhea, and constipation (rare)
  • Blood dyscrasias and blockade of cardiac H2 receptors (especially by intravenous administration) causing bradycardia and hypotension (rare); intravenous injections should therefore be given in intervals over 30 minutes.
  • Intravenous H2 blockers, especially cimetidine, may cause agitation, confusion, and hallucinations, especially in elderly patients or those with renal or hepatic insufficiency.
  • In critically ill patients, intravenous H2 blockers may increase the risk of nosocomial pneumonia.


With high doses or prolonged use, cimetidine can cause antiandrogenic side effects such as gynecomastia or impotence in men and galactorrhea in women by inhibiting the binding of dihydrotestosterone to androgen receptors, inhibiting estradiol metabolism, and increasing serum prolactin levels.

Cimetidine prolongs the half-lives of drugs such as warfarin, phenytoin, and clopidogrel by interfering with hepatic cytochrome P450 pathways.

Proton Pump Inhibitors

Proton pump inhibitors (PPIs) are lipophilic weak bases that are administered as inactive prodrugs and in delayed-release formulations. A PPI is absorbed from intestinal mucosa and diffuses readily into parietal cell canaliculi, where it becomes protonated and is concentrated by Henderson-Hasselbalch trapping. Here, it is converted into its active form, which irreversibly inactivates H+/K+-ATPase.

Esomeprazole is an S-isomer of omeprazole, while dexlansoprazole is an R-isomer of lansoprazole. Esomeprazole and pantoprazole are also available in intravenous-administration formulations.

PPIs are usually administered approximately one hour before a meal; their acid-inhibiting effects last for about 24 hours, and maximum effectiveness is achieved after 3–4 days of administration. PPIs undergo hepatic metabolism but have negligible renal clearance; hence, dose reduction is not required in renal insufficiency or in mild-to-moderate hepatic dysfunction.

PPIs inhibit both fasting- and meal-stimulated acid secretion and inhibit 90%–98% of a 24-hour acid secretion; they are therefore very effective in the management of gastrinoma and other conditions with acid hypersecretion compared with other classes of drugs.

PPIs are very safe; common adverse effects include headache, diarrhea, and abdominal pain. Rarely, cases of acute interstitial nephritis have been reported.

By reducing acid secretion, PPIs may reduce the absorption of vitamin B12 and calcium; hypomagnesemia has also been reported. Patients requiring long-term PPI treatment and who are at risk of osteoporosis should be monitored for bone density and given calcium supplements.

In patients taking PPIs, increased risk of community-acquired pneumonia, nosocomial pneumonia, Clostridium difficile infectionand other enteric infections have been reported.

Approximately 3% of patients taking PPIs develop hypergastrinemia, which normalizes within 4 weeks of stopping the drug. Enterochromaffin-like cell hyperplasia has also been reported, but carcinoid tumor formation has not been observed. Small benign gastric fundic gland polyps have been seen in some patients following long-term PPI intake.

Important drug interactions include the following:

  • PPIs interfere with the absorption of drugs such as ketoconazole, itraconazole, and digoxin by reducing gastric acidity.
  • PPIs (except rabeprazole and pantoprazole) may reduce the antiplatelet action of clopidogrel by reducing its activation.
  • Rabeprazole and pantoprazole do not have significant drug interactions.
  • Omeprazole may inhibit the metabolism of phenytoin, diazepam, and warfarin.
  • Esomeprazole inhibits the metabolism of diazepam.
  • Lansoprazole enhances the clearance of theophylline.

Mucosal Protective Agents


  • Sucralfate is an aluminum sucrose sulfate that acts by forming a viscous tenacious paste in water or acidic solutions; it selectively binds to erosions or ulcers for up to six hours. Negatively charged sucrose sulfate, a breakdown product of sucralfate, binds to positively charged proteins in the base of ulcers or erosions.
  • Sucralfate stimulates the secretion of mucosal bicarbonate and prostaglandins.
  • The drug is administered four times a day, approximately one hour before meals.
  • There are no systemic side effects due to a lack of systemic absorption. Because of the drug’s content of aluminum salt, an important side effect is constipation; thus, it should not be used for prolonged duration in patients with renal insufficiency.
  • Sucralfate reduces the absorption of many drugs by binding with them.

Prostaglandin Analogs

  • Misoprostol is a PGE1 analog with mucosal protective and acid inhibitory actions. It stimulates the production of mucus and bicarbonate and increases mucosal blood flow.
  • Misoprostol is used to prevent NSAID-induced ulcers, but requires dosing 3–4 times per day.
  • Important adverse effects are diarrhea and abdominal cramps.
  • As it stimulates uterine contractions, misoprostol should not be used during pregnancy and requires cautious use in women of childbearing age.
  • Misoprostol does not have significant drug interactions.

Bismuth Compounds

  • Bismuth subsalicylate and bismuth subcitrate potassium are bismuth compounds.
  • Bismuth subsalicylate is rapidly dissociated in the stomach; salicylate is absorbed and excreted in the urine, while 99% of bismuth is excreted in the stool. The minimally absorbed bismuth is stored in tissues and slowly excreted in the urine.
  • Bismuth compounds create a protective layer over erosions and ulcers and protect them from acid and pepsin. They also stimulate the secretion of mucus, bicarbonate, and prostaglandin.
  • As salicylate inhibits the secretion of prostaglandin and chloride in the intestines, bismuth subsalicylate reduces stool frequency and liquidity in acute infectious diarrhea.
  • Bismuth also has direct antimicrobial activity, including against H. pylori, and binds enterotoxins.
  • Bismuth compounds are used in the treatment of dyspepsia and acute diarrhea.
  • Bismuth compounds are included in 4-drug regimens for treatment of H. pylori-associated ulcers; however, triple-therapy regimens are considered first-line treatment.
  • Bismuth subsalicylate is also used in the prevention of traveler’s diarrhea.
  • Bismuth compounds are very safe, although harmless blackening of stool and darkening of the tongue may be seen.
  • Bismuth toxicity (encephalopathy) is not reported with bismuth subsalicylate or subcitrate, but prolonged use may cause salicylate toxicity.

Pharmacologic Management

Treatment of GERD

Infrequent dyspepsia or heartburn (< three per week) can be managed by taking an antacid or H2 blocker intermittently; frequent heartburn should be managed by twice-daily H2 blockers or PPIs.

Although antacids provide faster symptom relief, their effects are shorter lasting (1–2 hours) than those of H2 blockers (6–10 hours).

PPIs are more effective than H2 blockers in the management of gastroesophageal reflux disease; once-daily dosing is effective in approximately 85%–90% of patients. Long-term daily maintenance of PPIs is required in patients with erosive gastritis or esophageal complications of GERD, while those with an extraesophageal complication of GERD should be treated via twice-daily PPI administration for at least three months.

Treatment of Peptic Ulcers

  • PPIs have almost replaced H2 blockers in the management of peptic ulcers. However, H2 blockers, if used, are given as a once-daily bedtime dose for 6–8 weeks to suppress nocturnal acid secretion.
  • Most duodenal ulcers and gastric ulcers are healed by the use of PPIs for 4 weeks and 6–8 weeks, respectively.
  • Sucralfate accelerates the healing of and reduces the recurrence rate of peptic ulcers.
  • Following acute gastrointestinal bleeding from a peptic ulcer, high-dose oral PPIs or continuous intravenous infusion of PPIs is used to reduce the risk of rebleeding.

Treatment of H. pylori-associated Ulcers

The best regimen for the treatment of H. pylori-associated ulcers is 14-day triple therapy: a PPI (twice daily), clarithromycin (500 mg twice daily), and amoxicillin (1 g twice daily), followed by a PPI once daily for 4–6 weeks. Metronidazole (500 mg twice daily) can be used in penicillin-allergic patients.

An alternative 10-day regimen for treatment of H. pylori-associated ulcers is the administration of a PPI (twice daily) and amoxicillin (1 g twice daily) on days 1–5, followed by a PPI (twice daily), clarithromycin (500 mg twice daily), and tinidazole (500 mg twice daily) on days 6–10.

Both 14-day and 10-day regimens should be followed by a PPI once daily for 4–6 weeks to ensure complete healing of the ulcer.

Prevention of Bleeding from Stress-Related Gastritis in Critically Ill Patients

For patients without nasoenteric tubes or with significant ileus, intravenous H2 blockers are preferred over intravenous PPIs because of their cost-effectiveness and proven efficacy; continuous infusion is preferred over bolus administration.

In patients with nasoenteric tubes, immediate-release oral omeprazole is preferred over intravenous H2 blockers because of their cost-effectiveness and ease of administration.

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2 thoughts on “Drugs for Acid Peptic Diseases

  • Enrique Campos-Kaufman

    In the bismuth compund section, the 3rd and 4th bullet contradict themselves because first it says it enhances liberation of prostaglandins but then it says it inhibits it. I understand the first is caused by bismuth and the latter is caused by salycilate so, what happens at the end? is it the first effect or the latter effect?

    Thank you.

    1. Maria Jaehne

      Dear Enrique, thanks for your comment!

      Bismuth stimulates prostaglandin (PG) secretion, which is a protective factor for acid peptic disease. This is the reason why NSAIDs, which are PG-inhibitors, cause acid peptic diseases. Thus PG secretion in stomach is desirable property for a mucosal protective agent.
      Salicylates inhibit PG and Cl secretion in intestines, which is a desirable property to reduce stool output.
      Hence Bismuth subsalicylate is helpful in both acid peptic diseases, related to stomach, as well as in acute infections diarrhea, which occurs due to pathology in small intestine.

      I hope this will help to understand it better.

      Best regards,
      Maria from Lecturio.